Clinical Validity of a Prognostic Gene Expression Cluster-Based Model in Human Papillomavirus–Positive Oropharyngeal Carcinoma

Abstract

PURPOSE Under common therapeutic regimens, the prognosis of human papillomavirus (HPV)–positive squamous oropharyngeal carcinomas (OPCs) is more favorable than HPV-negative OPCs. However, the prognosis of some tumors is dismal, and validated prognostic factors are missing in clinical practice. The present work aimed to validate the prognostic significance of our published three-cluster model and to compare its prognostic value with those of the 8th edition of the tumor-node-metastasis staging system (TNM8) and published signatures and clustering models. METHODS Patients with HPV DNA-positive OPCs with locoregionally advanced nonmetastatic disease treated with curative intent (BD2Decide observational study, NCT02832102 ) were considered as validation cohort. Patients were treated in seven European centers, with expertise in the multidisciplinary management of patients with head and neck cancer. The median follow-up was 46.2 months (95% CI, 41.2 to 50), and data collection was concluded in September 2019. The primary end point of this study was overall survival (OS). Three-clustering models and seven prognostic signatures were compared with our three-cluster model. RESULTS The study population consisted of 235 patients. The three-cluster model confirmed its prognostic value. Two-year OS in each cluster was 100% in the low-risk cluster, 96.6% in the intermediate-risk cluster, and 86.3% in the high-risk cluster ( P = .00074). For the high-risk cluster, we observed an area under the curve = 0.832 for 2-year OS, significantly outperforming TNM 8th edition (area under the curve = 0.596), and functional and biological differences were identified for each cluster. CONCLUSION The rigorous clinical selection of the cases included in this study confirmed the robustness of our three-cluster model in HPV-positive OPCs. The prognostic value was found to be independent and superior compared with TNM8. The next step includes the translation of the three-cluster model in clinical practice. This could open the way to future exploration of already available therapies in HPV-positive OPCs tailoring de-escalation or intensification according to the three-cluster model.

A Clinically Translatable Immune-based Classification of HPV-associated Head and Neck Cancer with Implications for Biomarker-Driven Treatment Deintensification and Immunotherapy

“…immune rich: HR = 3.44, 95% CI 1.59 – 7.44, P = 0.002, univariate Cox model; Figure 1B,D, Supplementary Figure S5A ). In the prospective Big Data and Models for Personalized Head and Neck Cancer Decision Support (BD2Decide) study (n = 286, NCT02832102) of 286 locoregionally-advanced p16-positive patients treated homogeneously with radiation and/or chemotherapy at seven European institutions 32 , the immune classes exhibited distinct DFS ( P = 0.03, log rank test; immune desert vs . immune rich: HR = 2.6, 95% CI 1.1 – 5.7, P = 0.02, univariate Cox model; Figure 1A,C, Supplementary Figure S5C ) and OS ( P = 0.004, log rank test; immune desert vs .…”

“…Recurrence was defined as the presence of local, regional, or distant disease after completion of treatment. Detailed descriptions of all other cohorts have been provided elsewhere 30-32,52,53 . Treatments received for each cohort are described in Supplementary Table S2 .…”

Immune-based classification of HPV-associated oropharyngeal cancer with implications for biomarker-driven treatment de-intensification

“…The Cancer Genome Atlas (TCGA, n = 71), 35 Johns Hopkins University (JHU; n = 47), BD2Decide (n = 286), and Washington University (WashU) and Vanderbilt University (n = 262) cohorts are public HPV + OPSCC transcriptomic cohorts and have been described elsewhere. 36 , 37 , 38 , 39 , 40 Detailed descriptions of all other cohorts have been provided elsewhere. 36 , 37 , 38 , 39 , 40 Treatments received for each cohort are described in Supplementary Table S2 .…”

“… 36 , 37 , 38 , 39 , 40 Detailed descriptions of all other cohorts have been provided elsewhere. 36 , 37 , 38 , 39 , 40 Treatments received for each cohort are described in Supplementary Table S2 . All cohorts except for the TCGA cohort are HPV+ tumours solely from the oropharynx region.…”

Increased Abundances of CD16+ Non-Classical Monocytes Accompany with Elevated Monocytic PD-L1 and CD4+ T Cell Disturbances in Oropharyngeal Cancer

“…Various clinical and biological features such as the stage, site of disease, comorbidities, or human papilloma virus (HPV) status contribute to the alteration of different immune cells within the malignant transformation process [ 4 , 5 , 6 ]. In this context, HPV is a well-established causative factor, especially for oropharyngeal cancer (OPC) as it is the most common HPV-related malignancy of the head and neck [ 7 , 8 , 9 ]. Patients suffering from HPV-related oropharyngeal cancer are mostly younger and have a more favorable prognosis than nonvirally associated oropharyngeal cancer patients [ 10 , 11 ].…”